Haloperidol does not produce dopamine cell depolarization-block in paralyzed, unanesthetized rats.
A widely accepted theory postulates that chronic treatment with neuroleptics causes, in rats, the depolarization block of the majority of midbrain dopamine (DA) neurons. However, we reported that such treatment fails to reduce the number of spontaneously active DA neurons when the neuronal sampling is performed in the d-tubocurarine-paralyzed instead of chloral-hydrate anesthetized preparation. The present experiments were aimed at verifying whether the negative results might be due to the use of d-tubocurarine as paralyzing agent. Rats were chronically treated with haloperidol (0.5 mg kg-1 i.p., daily) for 3 to 4 weeks. Two to three hours after the last injection, the number of spontaneously active DA neurons in the ventral tegmental area (VTA) were sampled, and their discharging characteristics analyzed, both in animals under chloral hydrate anesthesia and in rats immobilized either with d-tubocurarine, gallamine or succinylcholine. The results indicate that chronic treatment with haloperidol reduced the number of spontaneously active VTA-DA neurons by about 65% in animals under chloral hydrate anesthesia, but failed to modify the number of spontaneously firing DA neurons in rats immobilized with d-tubocurarine, gallamine or succinylcholine. The results indicate that the depolarization block of DA neurons does not occur in the paralyzed preparation and raise doubts about the presence of this phenomenon in the intact non- anesthetized unrestrained animal.
Melis
M
M
Dept. of Neuroscience, 'Bernard B. Brodie,' University of Cagliari, via Porcell 4, I-09124 Cagliari, Italy.
Mereu
G
G
Lilliu
V
V
Quartu
M
M
Diana
M
M
Gessa
G L
GL
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002697:Chloral Hydrate; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005703:Gallamine Triethiodide; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents; D010243:Paralysis / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013390:Succinylcholine; D014403:Tubocurarine
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D002697:Chloral Hydrate; D013390:Succinylcholine; D006220:Haloperidol; D005703:Gallamine Triethiodide; D014403:Tubocurarine